Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Comprehensive elucidation of resting-state functional connectivity in anorexia nervosa by a multicenter cross-sectional study.

BACKGROUND: Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs). METHODS: We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons. RESULTS: Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction). CONCLUSION: Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Measurement of work-related psychological injury with depressive symptoms.

OBJECTIVE: This study aimed to measure the level of psychological injury caused by work-related stress as well as the severity of depression among workers. METHOD: First, we conducted an online survey and recruited 500 workers diagnosed with depression or adjustment disorder to investigate what type of stress they experienced within six months before onset. Second, we conducted another online survey and recruited 767 participants who experienced some form of work-related stress. All the participants were classified into four groups by whether or not they were diagnosed with depression and whether or not they quit their jobs due to work-related stress. We used the Impact of Event Scale-Revised (IES-R) to measure psychological injury caused by work-related stressful events and the Patient Health Questionnaire (PHQ)-9 to assess the severity of depression. RESULTS: In study 1, 62.4% of workers diagnosed with depression or adjustment disorder experienced work-related stress within six months before onset. In study 2, the IES-R mean scores were 40.7 (SD = 23.1) for Group A (workers with depression and quit their jobs) and 36.67 (SD = 23.4) for Group B (workers with depression but stayed at their jobs), with both exceeding the cut-off point (24/25) of PTSD (Post-Traumatic Stress Disorder), while the mean score of Group C (workers who did not have depression but quit their jobs because of work-related stress) was 20.74 (SD = 21.2), and it was 13.89 (SD = 17.4) for Group D (workers who had work-related stress but stayed at their jobs), with both of them below the cut-off point of PTSD. The total scores of IES-R of Group A and Group B were significantly higher than those of Group C and Group D(p < 0.001). There was a significant positive correlation between the scores of IES-R and PHQ-9 for all four groups (r = 0.708). CONCLUSIONS: This study suggests that it is necessary to measure not only depressive symptoms but also the level of psychological injury resulting from stressful events in the workplace to assess workers with depression.

Cognitive behavior therapy for autistic adolescents, awareness and care for my autistic traits program: a multicenter randomized controlled trial.

BACKGROUND: Autistic people demonstrate focused interests, sensitivity to sensory stimulation, and, compared with the general population, differences in social communication and interaction. We examined whether a combination of the Awareness and Care for My Autistic Traits (ACAT) program and treatment-as-usual is more effective than only treatment-as-usual in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among autistic adolescents and their parents/guardians. METHODS: Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and treatment-as-usual or only treatment-as-usual. The combined group received six weekly 100-minute ACAT sessions, while the treatment-as-usual group received no additional intervention. The primary outcome was the change in understanding of autistic attributes (Autism Knowledge Quiz-Child), administered from pre- to post-intervention. The secondary outcomes included the change in Autism Knowledge Quiz-Parent, reduced treatment stigma, and improved mental health and social adaptation among autistic adolescents and their parents/guardians. A primary outcome measure scale was scored by assessors who were blind to the group assignment. RESULTS: The combined group (both autistic adolescents and their parents/guardians) showed an increase in Autism Knowledge Quiz scores compared to those in the treatment-as-usual group. Autistic adolescents in the combined group also demonstrated a decrease in treatment-related stigma and an improvement in general mental health compared to those in the treatment-as-usual group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, general mental health, adaptive skills, or attitudes toward their children. CONCLUSIONS: The ACAT program could be an effective treatment modality to increase the understanding of autistic attributes among both autistic adolescents and their parents/guardians. The ACAT program positively affects self-understanding, reduces treatment stigma, and stabilizes behavioral issues for autistic adolescents as a part of mental health measures, but it does not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial. TRIAL REGISTRATION: The study was registered in UMIN (UMIN000029851, 06/01/2018).

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

The mediating effect of symptoms of posttraumatic stress disorder and depression on the relationship between personality traits and quality of life in emergency service workers.

BACKGROUND: Emergency service workers are often exposed to fatalities during accidents or disasters. Therefore, they may be more prone to experiencing posttraumatic stress disorder (PTSD) and depression. It has been shown that these comorbid disorders are related to personality traits and quality of life (QOL). METHODS: We hypothesized that mental disorders, such as symptoms of PTSD and depression, mediate the relationship between personality traits, as measured on the 10-Item Personality Inventory (TIPI), and QOL, as measured on the MOS 36-item Short-Form Health Survey (SF-36). RESULTS: Participants were aged 23-61 years. Questionnaires were sent to 373 participants, 220 of whom returned responses. A direct effect was found between two subscales of the TIPI (Extraversion and Emotional stability) and mental component summary scores of the SF-36 (Extraversion: ß = 0.154, p < .001; Emotional stability: ß = 0.179, p < .001), which indicated partial mediation. A significant indirect effect was revealed between two personality traits and mental health summary scores (Extraversion: ß = 0.058, p < .001; Emotional stability: ß = 0.087, p < .001). We also found a direct effect of extraversion scores of the TIPI on role/social component summary scores of the SF-36 (ß = 0.084, p < .05). However, none of the 95% confidential intervals was significant, which indicated full mediation, and the indirect effect was significant (ß = 0.023, p < .01). Sensitivity analysis indicated that a direct effect between extraversion scores of the TIPI and role/social component summary scores of the SF-36 was significant, which indicated partial mediation. CONCLUSIONS: The findings of direct and indirect effects highlight the importance of identifying effective methods for protecting individuals from developing symptoms of PTSD and depression; moreover, they may help improve QOL. The capacity of dealing with incidents among emergency service workers may vary depending on their personality traits. Therefore, the screening of mental health states that includes a personality trait inventory may be valuable.

Effectiveness of Unguided Internet-Based Cognitive Behavioral Therapy and the Three Good Things Exercise for Insomnia: 3-Arm Randomized Controlled Trial.

BACKGROUND: The treatment of insomnia with sleep medication causes problems such as long-term use, dependence, and significant economic losses, including medical expenses. Evidence-based lifestyle guidance is required to improve insomnia symptoms not only in person but also in easy-to-use web-based formats. OBJECTIVE: This study aims to clarify whether unguided internet-based cognitive behavioral therapy (ICBT) or the Three Good Things (TGT) exercise, both administered as self-help internet interventions without email support, could improve insomnia symptoms compared with a waiting list control (WLC) group. METHODS: A 4-week program was implemented, and participants were randomly allocated to 1 of the 3 groups. The primary outcome measure was the Pittsburgh Sleep Questionnaire (PSQI) score at 4 weeks compared with baseline. RESULTS: Of the 21,394 individuals invited to participate, 312 (1.46%) met the eligibility criteria and were randomly assigned to 1 of the 3 groups. Of these 312 individuals, 270 (86.5%; ICBT 79/270, 29.3%; TGT 88/270, 32.6%; and WLC 103/270, 38.1%) completed a postintervention survey at 4 and 8 weeks. The adjusted mean changes of the primary outcome measure (PSQI) in the ICBT (-1.56, 95% CI -2.52 to -0.59; P<.001) and TGT (-1.15, 95% CI -2.08 to -0.23; P=.002) groups at 4 weeks from baseline showed a significant improvement compared with the WLC group. The adjusted mean changes in the secondary outcome measures of sleep onset latency, total sleep time, Athens Insomnia Scale score, and Patient Health Questionnaire-9 score at 4 weeks from baseline, as well as in the PSQI at 8 weeks from baseline, showed significant improvement for ICBT. Moreover, total sleep time, Athens Insomnia Scale, and Patient Health Questionnaire-9 scores at 4 weeks from baseline showed a significant improvement in the TGT group compared with the WLC group. CONCLUSIONS: A total of 4 weeks of unguided ICBT and TGT exercises improved insomnia. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry UMIN000034927; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039814.

The Screening Test for Aphasia and Dysarthria (STAD) for Patients with Neurological Communicative Disorders: A Large-Scale, Multicenter Validation Study in Japan.

INTRODUCTION: Evaluation of multiple domains, such as language, articulation, and cognitive function, is frequently required in neurological communicative disorders. The purpose of this study was to investigate the performance of a 10-min screening scale for estimating aphasia, dysarthria, and cognitive dysfunction using a multicenter, large-sized consecutive series. METHODS: We conducted a multicenter validation study that included 314 patients with brain injury between February 1 and June 31, 2018, from 20 medical centers across Japan. The Screening Test for Aphasia and Dysarthria (STAD) was developed in Japan in 2009, and a previous smaller-scale retrospective study established its high to moderate validity. All patients had undergone the STAD, and 212 of them underwent the Western Aphasia Battery or Assessment of Motor Speech for Dysarthria. The effect size on all 29 items and receiver operating curves of 3 sections of the STAD were analyzed based on external criteria, which were decided considering the clinical diagnosis of aphasia, dysarthria, and cognitive dysfunction. Correlations between the STAD and reference tests were calculated. RESULTS: The phi coefficients of 23 out of 29 items exceeded the moderate effect size of 0.3 toward the targeted disorder. Overall, there was a good balance between sensitivity (82-92%) and specificity (77-78%), with moderate to large positive and negative likelihood ratios (3.7-4.19 and 0.1-0.23). The Pearson's r between the verbal section and Western Aphasia Battery Aphasia Quotient, the articulation section and Assessment of Motor Speech for Dysarthria, and the nonverbal section and Western Aphasia Battery Nonlinguistic Skills were 0.89, 0.70, and 0.79, respectively. CONCLUSION: We demonstrated that the STAD has acceptable content and concurrent validity for the assessment of communicative function in patients with brain injury. This short screening tool can be useful in specific contexts, such as in early bedside investigations, to obtain a quick summary of communicative function prior to the administration of other tests, and in cases where more in-depth testing is not feasible.

Calculation of Stopping-Power Ratio from Multiple CT Numbers Using Photon-Counting CT System: Two- and Three-Parameter-Fitting Method.

The two-parameter-fitting method (PFM) is commonly used to calculate the stopping-power ratio (SPR). This study proposes a new formalism: a three-PFM, which can be used in multiple spectral computed tomography (CT). Using a photon-counting CT system, seven rod-shaped samples of aluminium, graphite, and poly(methyl methacrylate) (PMMA), and four types of biological phantom materials were placed in a water-filled sample holder. The X-ray tube voltage and current were set at 150 kV and 40 µA, respectively, and four CT images were obtained at four threshold settings. A semi-empirical correction method that corrects the difference between the CT values from the photon-counting CT images and theoretical values in each spectral region was also introduced. Both the two- and three-PFMs were used to calculate the effective atomic number and electron density from multiple CT numbers. The mean excitation energy was calculated via parameterisation with the effective atomic number, and the SPR was then calculated from the calculated electron density and mean excitation energy. Then, the SPRs from both methods were compared with the theoretical values. To estimate the noise level of the CT numbers obtained from the photon-counting CT, CT numbers, including noise, were simulated to evaluate the robustness of the aforementioned PFMs. For the aluminium and graphite, the maximum relative errors for the SPRs calculated using the two-PFM and three-PFM were 17.1% and 7.1%, respectively. For the PMMA and biological phantom materials, the maximum relative errors for the SPRs calculated using the two-PFM and three-PFM were 5.5% and 2.0%, respectively. It was concluded that the three-PFM, compared with the two-PFM, can yield SPRs that are closer to the theoretical values and is less affected by noise.

Predictors of response to exposure and response prevention-based cognitive behavioral therapy for obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT), which includes exposure and response prevention (ERP), is effective in improving symptoms of obsessive-compulsive disorder (OCD). However, whether poor cognitive functions and autism spectrum disorder (ASD) traits affect the therapeutic response of patients with OCD to ERP-based CBT remains unclear. This study aimed to identify factors predictive of the therapeutic response of Japanese patients with OCD to ERP-based CBT. METHODS: Forty-two Japanese outpatients with OCD were assessed using the Wechsler Adult Intelligence Scale-III (WAIS-III), Yale-Brown Obsessive-Compulsive Scale, Patient Health Questionnaire 9-item scale, and Autism Spectrum Quotient (AQ) at pre- and post-treatment. We used multiple regression analyses to estimate the effect on therapeutic response change. The treatment response change was set as a dependent variable in multiple regression analyses. RESULTS: Multiple regression analyses showed that among independent variables, communication as an AQ sub-scale and Letter Number Sequencing as a WAIS-III sub-test predict the therapeutic response to ERP-based CBT . CONCLUSIONS: Our results suggest that diminished working memory (Letter Number Sequencing), poor communication skill (AQ sub-scale) may undermine responsiveness to ERP-based CBT among patients with OCD. TRIAL REGISTRATION: UMIN, UMIN00024087 . Registered 20 September 2016 - Retrospectively registered (including retrospective data).

Hemodynamic responses in prefrontal cortex and personality characteristics in patients with bulimic disorders: a near-infrared spectroscopy study.

PURPOSE: This study sought to identify the prefrontal cortex hemodynamic response that is dependent on cognitive performance in patients with bulimic disorders (BD), and investigate its association with personality characteristics. METHODS: Nineteen female patients with BD and 23 healthy women were recruited. Their personality characteristics related to eating disorders were examined using a self-reporting questionnaire, namely the eating disorder inventory-2 (EDI-2). Cerebral blood flow response in the prefrontal cortex during the digit span backward task (DSBT) was measured using near-infrared spectroscopy (NIRS). Change in oxygenated hemoglobin concentration (ΔoxyHb), obtained using NIRS, were used as an index of brain activity. Further, the relationship between prefrontal cortical activity and personality characteristics was investigated in patients with BD. RESULTS: The cognitive performance of patients with BD was significantly lower in the DSBT compared with healthy subjects. There was no difference between the groups in ΔoxyHb during the task. Task scores of patients with BD correlated with asceticism and perfectionism. Moreover, the asceticism score was negatively correlated with ΔoxyHb of the bilateral prefrontal cortex in patients with BD. CONCLUSION: The results suggest that cognitive performance and brain activity induced during DSBT might be affected by asceticism in BD patients. LEVEL OF EVIDENCE: III, case-control study.

Investigation of the BOLD and CBV fMRI responses to somatosensory stimulation in awake marmosets (Callithrix jacchus).

Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marmosets (Callithrix jacchus), a New World non-human primate with a lissencephalic brain and with growing use in biomedical research. The marmosets were acclimatized to head fixation and placed in a 7-T magnetic resonance imaging (MRI) scanner. Somatosensory stimulation (333-µs pulses; amplitude, 2 mA; 64 Hz) was delivered bilaterally via pairs of contact electrodes. A block design paradigm was used in which the stimulus duration increased in pseudo-random order from a single pulse up to 256 electrical pulses (4 s). For CBV measurements, 30 mg/kg of ultrasmall superparamagnetic ironoxide particles (USPIO) injected intravenously, were used. Robust BOLD and CBV HRFs were obtained in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2) and caudate at all stimulus conditions. In particular, BOLD and CBV responses to a single 333-µs-long stimulus were reliably measured, and the CBV HRF presented shorter onset time and time to peak than the BOLD HRF. Both the size of the regions of activation and the peak amplitude of the HRFs grew quickly with increasing stimulus duration, and saturated for stimulus durations greater than 1 s. Onset times in S1 and S2 were faster than in caudate. Finally, the fine spatiotemporal features of the HRF in awake marmosets were similar to those obtained in humans, indicating that the continued refinement of awake non-human primate models is essential to maximize the applicability of animal functional MRI studies to the investigation of human brain function.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

AIM: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. METHODS: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. RESULTS: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. CONCLUSION: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

OBJECTIVE: To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. METHODS: We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. RESULTS: There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. CONCLUSION: Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Cognitive Behavioral Therapy for Patients with Social Anxiety Disorder Who Remain Symptomatic following Antidepressant Treatment: A Randomized, Assessor-Blinded, Controlled Trial.

BACKGROUND: Although antidepressants are still a commonly used treatment for social anxiety disorder (SAD), a significant proportion of patients fail to remit following antidepressants. However, no standard approach has been established for managing such patients. This study aimed to examine the effectiveness of cognitive behavioral therapy (CBT) as an adjunct to usual care (UC) compared with UC alone in SAD patients who remain symptomatic following antidepressant treatment. METHODS: This was a prospective randomized open-blinded end-point study with two parallel groups (CBT + UC, and UC alone, both for 16 weeks) conducted from June 2012 to March 2014. SAD patients who remain symptomatic following antidepressant treatment were recruited, and a total sample size of 42 was set based on pilot results. RESULTS: Patients were randomly allocated to CBT + UC (n = 21) or UC alone (n = 21). After 16 weeks, adjusted mean reduction in the Liebowitz Social Anxiety Scale from baseline for CBT + UC and UC alone was -40.87 and 0.68, respectively; the between-group difference was -41.55 (-53.68 to -29.42, p < 0.0001). Response rates were 85.7 and 10.0% for CBT + UC and UC alone, respectively (p < 0.0001). The corresponding remission rates were 47.6 and 0.0%, respectively (p = 0.0005). Significant differences were also found in favor of CBT + UC for social anxiety symptoms, depressive symptoms, and functional impairment. CONCLUSIONS: Our results suggest that in SAD patients who have been ineffectively treated with antidepressants, CBT is an effective treatment adjunct to UC over 16 weeks in reducing social anxiety and related symptoms.

Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study.

Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN.